A combination of an iron chelator with an antioxidant effectively diminishes the dendritic loss, tau-hyperphosphorylation, amyloids-β accumulation and brain mitochondrial dynamic disruption in rats with chronic iron-overload

Sripetchwandee, Jirapas; Wongjaikam, Suwakon; Krintratun, Warunsorn; Chattipakorn, Nipon

doi:10.1016/j.neuroscience.2016.07.003

Cited by 75 publications

(56 citation statements)

References 56 publications

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“…ROS produced by iron also reacts with the cell membrane and causes lipid peroxidation. During this reaction, ROS generates toxic aldehyde products, including malondialdehyde and 4-hydroxylnonenal [19]. These toxic components react with proteins to produce carbonyl functions, which damage the proteins.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, increased iron level in the brain suppresses occludin expression. Given the role of occluding, a protein of tight junction, in the BBB, reducing its expression may disturb the function of BBB and thus damage the brain [19]. Although, iron is essential for many metabolic processes, excess iron can be toxic to the brain.…”

Section: Resultsmentioning

confidence: 99%

“…Iron accumulation and protein aggregation, both result in extensive oxidative stress, which disturbs synaptic function [16]. Furthermore, iron accumulation leads to loss of dendritic spines [19], which contributes to a number of neuropsychiatric disorders [33]. Thus we propose that iron accumulation has a role in cognitive suppression in AD.…”

Section: Resultsmentioning

confidence: 99%

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Iron oxide nanoparticles may damage to the neural tissue through iron accumulation, oxidative stress, and protein aggregation

et al. 2017

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BackgroundIn the recent decade, iron oxide nanoparticles (IONPs) have been proposed for several applications in the central nervous system (CNS), including targeting amyloid beta (Aβ) in the arteries, inhibiting the microglial cells, delivering drugs, and increasing contrast in magnetic resonance imaging. Conversely, a notable number of studies have reported the role of iron in neurodegenerative diseases. Therefore, this study has reviewed the recent studies to determine whether IONPs iron can threaten the cellular viability same as iron.ResultsIron contributes in Fenton’s reaction and produces reactive oxygen species (ROS). ROS cause to damage the macromolecules and organelles of the cell via oxidative stress. Iron accumulation and oxidative stress are able to aggregate some proteins, including Aβ and α-synuclein, which play a critical role in Alzheimer’s and Parkinson’s diseases, respectively. Iron accumulation, oxidative stress, and protein aggregation make a positive feedback loop, which can be toxic for the cell. The release of iron ions from IONPs may result in iron accumulation in the targeted tissue, and thus, activate the positive feedback loop. However, the levels of IONPs induced toxicity depend on the size, concentration, surface charge, and the type of coating and functional groups of IONPs.ConclusionIONPs depending on their properties can lead to iron accumulation, oxidative stress and protein aggregation in the neural cells. Therefore, in order to apply IONPs in the CNS, the consideration of IONPs properties is crucial.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Iron oxide nanoparticles may damage to the neural tissue through iron accumulation, oxidative stress, and protein aggregation

et al. 2017

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“…Interestingly, our recent studies found that the combination of an oral iron chelator DFP and an antioxidant NAC could improve and restore normal brain and heart function effectively and provided more robust results than either DFO, DFP, DFX or NAC alone in the iron-overloaded rat model4042. Consistently in the present study, a combination of DFP plus NAC provided more effective results than either DFO, DFP, DFX, or NAC alone in restoring cardiac [Ca 2+ ]i homeostasis leading to restored normal cardiac contractility and LV function by increased %LVEF to a normal condition in iron-overloaded rats.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, growing evidence indicates that N-acetyl cysteine (NAC) has an iron chelating property38, and is a potent antioxidant which is used to treat children with β-thalassemia39. Moreover, our recent study also found that combined DFP plus NAC had synergistic beneficial effects in restoring function to the brain4041 and heart42 in iron-overloaded rats. However, the effects of combining an oral iron chelator DFP and an antioxidant NAC on cardiac [Ca 2+ ]i homeostasis as well as the impact of this treatment on calcium cycling and iron regulatory proteins in iron-overloaded rats have never been investigated.…”

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confidence: 89%

Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine

Wongjaikam

Kumfu

Khamseekaew

et al. 2017

Sci Rep

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Intracellular calcium [Ca2+]i dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca2+]i homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months. At 2 months, HFe rats were divided into 6 groups and treated with either a vehicle, DFO (25 mg/kg/day), DFP (75 mg/kg/day), DFX (20 mg/kg/day), NAC (100 mg/kg/day), or combined DFP plus NAC. At 4 months, the number of cardiac T-type calcium channels was increased, whereas cardiac sarcoplasmic-endoplasmic reticulum Ca2+ ATPase (SERCA) was decreased, leading to cardiac iron overload and impaired cardiac [Ca2+]i homeostasis. All pharmacological interventions restored SERCA levels. Although DFO, DFP, DFX or NAC alone shared similar efficacy in improving cardiac [Ca2+]i homeostasis, only DFP + NAC restored cardiac [Ca2+]i homeostasis, leading to restoring left ventricular function in the HFe-fed rats. Thus, the combined DFP + NAC was more effective than any monotherapy in restoring cardiac [Ca2+]i homeostasis, leading to restored myocardial contractility in iron-overloaded rats.

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Atrial fibrillation in β‐thalassemia patients with a focus on the role of iron‐overload and oxidative stress: A review

Nomani

Bayat

Sahebkar

et al. 2018

Journal Cellular Physiology

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Cardiac complications including arrhythmia and especially atrial fibrillation (AF) are common causes of death in β‐thalassemia patients. The main factor in the etiopathogenesis of these complications is iron overload, which results in increased oxidative stress. Although there is a known association between cardiac complications and iron overload in β‐thalassemia patients, there is no comprehensive review on AF and excessive iron with a focus on oxidative stress in these patients. The aim of this article was to review the different aspects of AF in β‐thalassemia patients with a focus on the prevention and treatment of AF by using iron chelators and/or anti‐oxidants. AF in β‐thalassemia patients is more common than in the general population. One of the most important causes of AF is cardiac iron overload and the harmful effects of increased oxidative stress. Iron‐induced AF can be reversed by using an intensive iron chelation regimen. Based on a few experimental studies, the combination of iron chelators with some anti‐oxidants, including NAC, vitamin C, and acetaminophen, can lead to improved cardiac protection. However, the effect of such combinations on cardiac arrhythmias should be further evaluated with animal and human studies.

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A combination of an iron chelator with an antioxidant effectively diminishes the dendritic loss, tau-hyperphosphorylation, amyloids-β accumulation and brain mitochondrial dynamic disruption in rats with chronic iron-overload

Cited by 75 publications

References 56 publications

Iron oxide nanoparticles may damage to the neural tissue through iron accumulation, oxidative stress, and protein aggregation

Iron oxide nanoparticles may damage to the neural tissue through iron accumulation, oxidative stress, and protein aggregation

Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine

Atrial fibrillation in β‐thalassemia patients with a focus on the role of iron‐overload and oxidative stress: A review

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